Cohn Melvin
Conceptual Immunology Group, The Salk Institute, 10010 North Torrey Pines Road, La Jolla, CA, 92037, USA.
Immunol Res. 2016 Aug;64(4):795-803. doi: 10.1007/s12026-016-8796-8.
There are only two comprehensive models attempting to account for the TCR structure-function relationships, referred to as the Standard or Centric model (Model I) and the Tritope model (Model II). This essay is written to analyze comparatively the two formulations of restrictive reactivity, stressing in particular the logic of each. Model I is essentially built on an analogy between the TCR and the BCR. Given a TCR with only one combining site (paratope), restrictive recognition requires that its ligand be viewed as a composite structure between the peptide and restricting element. It is this relationship that entrains a set of correlates that makes Model I untenable. Model II is predicated on the postulate that the recognition of the allele-specific determinants expressed by MHC-encoded restricting elements (R) is germline encoded and selected, whereas the recognition of peptide (P) is somatically encoded and selected. These selective pressures must operate on definable structures and this, in turn, necessitates a multiply recognitive T cell antigen receptor (TCR) with independent anti-R and anti-P paratopes that function coherently to signal restrictive reactivity. The consequences of this "two repertoire" postulate give us a concept of TCR structure quite distinct from that at present generally accepted, as well as a surprising relationship between numbers of functional TCR V gene segments and allele-specific determinants in the species. In the end, both models must deal with the relationship between the epitope-paratope interaction(s) and the signals to the T cell necessary for its differentiation and function.
仅有两种综合模型试图解释TCR的结构-功能关系，分别称为标准或中心模型（模型I）和三表位模型（模型II）。本文旨在对两种限制性反应性的表述进行比较分析，尤其强调每种表述的逻辑。模型I本质上是基于TCR和BCR之间的类比构建的。对于只有一个结合位点（互补决定区）的TCR，限制性识别要求其配体被视为肽与限制性元件之间的复合结构。正是这种关系引发了一系列相互关联的因素，使得模型I难以成立。模型II基于这样一个假设，即对由MHC编码的限制性元件（R）所表达的等位基因特异性决定簇的识别是由种系编码并选择的，而对肽（P）的识别是由体细胞编码并选择的。这些选择压力必须作用于可定义的结构，这反过来又需要一个具有独立的抗R和抗P互补决定区的多重识别性T细胞抗原受体（TCR），它们协同发挥作用以发出限制性反应性的信号。这种“两个库”假设的结果为我们提供了一个与目前普遍接受的TCR结构概念截然不同的概念，以及该物种中功能性TCR V基因片段数量与等位基因特异性决定簇之间令人惊讶的关系。最后，两种模型都必须处理表位-互补决定区相互作用与T细胞分化和功能所需信号之间的关系。
